Participation of the neutrophin brain-derived neurotrophic factor in neuropsychiatric systemic lupus erythematosus

Tamashiro, Leticia; Oliveira, Renê Donizeti Ribeiro de; Oliveira, Rodrigo Mota de; Frota, Elizabeth Regina Comini; Donadi, Eduardo Antônio; Del-Ben, Cristina Marta; Teixeira, Antônio Lúcio; Louzada‐Júnior, Paulo

doi:10.1093/rheumatology/keu251

Cited by 18 publications

(16 citation statements)

References 42 publications

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“…It was previously shown that plasma BDNF was increased in inactive SLE as compared with active disease, and thus it was suggested as a possible marker of response to treatment [27]. In the same study, a negative correlation between serum BDNF and the SLEDAI score was noted, which was confirmed by another group [28].…”

Section: Discussionsupporting

confidence: 53%

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Kalinowska-Łyszczarz

Pawlak

Wyciszkiewicz

et al. 2017

Neuroimmunomodulation

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Objective: Central nervous system (CNS) involvement in systemic lupus erythematosus (SLE) remains poorly understood. Damage within the CNS is driven by the autoimmune response; however, immunopathophysiology of neuropsychiatric (NP) SLE is multifactorial. Immune cell neurotrophin production could be neuroprotective against autoimmunity-driven CNS damage, as has been shown in multiple sclerosis. The aim of this study was to establish whether immune cell neurotrophin production is associated with damage severity in NPSLE. Methods: Selected neurotrophins (BDNF, NGF, NT-3, and NT-4/5) were measured with ELISA within peripheral blood mononuclear cells (PBMCs) isolated from 38 NPSLE patients matched with 39 healthy controls. Subcortical and cortical structure volumes were segmented with the Freesurfer 5.3 pipeline on T1-weighted isotropic images acquired on a 1.5-T MRI scanner. Results: BDNF and NGF levels in PBMCs were reduced in NPSLE compared to the healthy population. The PBMC BDNF level was associated with reduced thalamus, caudate, and putamen volumes. The NGF level correlated with lateral ventricles enlargement and thalamic volume loss. Conclusions: In NPSLE, immune cell BDNF and NGF levels are linked with subcortical atrophy. Higher BDNF levels are associated with higher midsagittal atrophy, which may reflect compensatory mechanisms, upregulating BDNF when neuroprotection is needed. These data require further confirmation.

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Section: Discussionsupporting

confidence: 53%

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Kalinowska-Łyszczarz

Pawlak

Wyciszkiewicz

et al. 2017

Neuroimmunomodulation

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“…Dysregulation of Neurotrophin/ TRK signaling pathway in anti-dsDNA + subgroup as observed in this study have been reported to be associated with T-cell development [34] and neuronal functions [35]. Neurotrophins were reported in neuropsychiatric SLE (NPSLE) patients and its increased expression was associated with improved neuropsychiatric symptoms [36] but no association has been reported in SLE patient with specific serological group.…”

Section: Discussionmentioning

confidence: 71%

RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities

et al. 2016

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Systemic lupus erythematosus (SLE) patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA) only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA). Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA) software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways with the uniquely expressed transcripts in each SLE subgroup indicates that specific immunological disease mechanisms are operative in distinct SLE patients’ subsets. This ‘sub-grouping’ approach could further be useful for clinical evaluation of SLE patients and devising targeted therapeutics.

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“…Ikenouchi-Sugita et al ( 54 ) and Ikenouchi et al ( 56 ) suggested that plasma BDNF levels and the catecholamine metabolites have a higher predictive value regarding the severity of psychotic symptoms in SLE, offering an alternate diagnosis to steroid-induced psychosis. Of note, Tamashiro et al ( 55 ) demonstrated that increased plasma BDNF levels did not correlate with CNS lesions, which contradicts previous studies. In addition, they proved a negative correlation between plasma BDNF levels and SLEDAI and a positive correlation with the levels of complements and the numbers of circulatory lymphocytes.…”

Section: Bdnf In Autoimmune Inflammatory Diseasesmentioning

confidence: 82%

Brain‑derived neurotrophic factor in autoimmune inflammatory diseases (Review)

Wang

Tian

2021

Exp Ther Med

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Numerous recent studies reported that brain-derived neurotrophic factor (BDNF) also exists in the peripheral blood to regulate the proliferation, differentiation and survival of lymphocytes. Besides the role of BDNF in neuron repair, circulatory BDNF also enhances the proliferation and reduces apoptosis of lymphocytes. Peripheral lymphocytes express both BDNF and its receptors. Increasing evidence has indicated that altered BDNF serum levels significantly affect patients with autoimmune inflammatory diseases and may also be linked to the pathogenesis of diseases. For instance, systemic lupus erythematosus, an autoimmune inflammatory disease involving multiple organs, is frequently linked to altered B lymphocyte function, imbalance of T-cell subpopulations and loss of immune tolerance, which dysregulates the immune regulatory network with excessive secretion of inflammatory cytokines. The present review summarized studies that suggest a potential link between circulatory BDNF and autoimmune inflammatory diseases.

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Participation of the neutrophin brain-derived neurotrophic factor in neuropsychiatric systemic lupus erythematosus

Abstract: Plasma BDNF level is increased in SLE patients and this increase is independent of the occurrence of NP manifestations. In addition, plasma BDNF levels increased with control of SLE activity, which points to the potential use of BDNF as a biomarker of response to treatment.

Cited by 18 publications

References 42 publications

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

Immune Cell Neurotrophin Production Is Associated with Subcortical Brain Atrophy in Neuropsychiatric Systemic Lupus Erythematosus Patients

RNA-seq Analysis Reveals Unique Transcriptome Signatures in Systemic Lupus Erythematosus Patients with Distinct Autoantibody Specificities

Brain‑derived neurotrophic factor in autoimmune inflammatory diseases (Review)

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